Ablation of the ATP-binding cassette transporter, Abca2 modifies response to estrogen-based therapies.

摘要: The ATP-binding cassette transporter 2 (ABCA2) is an endolysosomal protein expressed in oligodendrocytes and Schwann cells, prostate, ovary macrophages. In cell cultures, ABCA2 over-expression has been linked with resistance to the anticancer agent, estramustine phosphate (EMP; a nor-nitrogen mustard conjugate of estradiol). present study shows that Abca2 knockout (KO) mice have greater sensitivity variety side effects induced by EMP treatment. Chronic (12 × 100 mg/kg body weight) produced mortality 36% KO mice, but only 7% age-matched wild type (WT). Side drug were also more prevalent mouse. For example, during first week treatments, 67% males (compared 6% WT males) responded episodic erectile events. localized within pene corpuscles, (which rely on modified cells for amplification tactile signals) suggesting may function process. Endothelial nitric oxide synthase (eNOS; source response) levels similar male penile tissue. Treatment (once daily four days) elevated serum estradiol estrone both KO. However, circulating these estrogens higher implying reduced plasma clearance as consequence ablation. Consistent pro-convulsant estrogens, displayed increased incidence seizures following (14% vs. 0%). Taken together, data indicate deficiency renders sensitive treatment-induced role regulating transport and/or metabolism.